title: The promises of PCSK9 inhibition.
abstract: OBJECTIVE
  In the past 10 years, the LDL receptor inhibitor proprotein convertase subtilisin kexin type 9 (PCSK9) has emerged as a validated target for lowering plasma LDL cholesterol levels. Here we review the most recent reports on PCSK9 out of a total of 500 publications published in print or online before March 2013 and indexed on PubMed.
  
  
  RESULTS
  All published in 2012, phase I and II clinical trials demonstrate that fully human monoclonal antibodies targeting PCSK9 dramatically reduce LDL-C and enable patients to reach their target goals, without severe or serious safety issues.
  
  
  CONCLUSIONS
  This review summarizes the discovery of PCSK9, its original mode of action as a secreted inhibitor of the LDL receptor, as well as its genetic regulation by statins. We then focus on the major results from the 2012 phase I and II PCSK9 inhibitor clinical trials. We also review the recent in-vivo studies demonstrating the potential cardiovascular benefits of long-term PCSK9 inhibition and discuss its potential side-effects.
authors.affiliation: The University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Francine
authors.initials: F
authors.lastname: Petrides
authors.forename: Kate
authors.initials: K
authors.lastname: Shearston
authors.forename: Mathias
authors.initials: M
authors.lastname: Chatelais
authors.forename: Florian
authors.initials: F
authors.lastname: Guilbaud
authors.forename: Olivier
authors.initials: O
authors.lastname: Meilhac
authors.forename: Gilles
authors.initials: G
authors.lastname: Lambert
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000201:enzymology; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab; C571059:alirocumab